Elucidation of the cellular and molecular mechanisms which determine the expressed antibody repertoire remains a major challenge in immunology. Knowledge of V gene diversity, organization, and expression is important to an understanding of the formation of the antibody repertoire in normal as well as diseased states. In the last few years, great advances have been made in our understanding of t...

We have cloned and sequenced a full length human immunoglobulin M chain cDNA of the membrane bound form. The variable region, nucleotides 119 to 529, is a member of the VHj family. Nucleotides 530 through 1831 encode the heavy chain constant region, which shows 73% identity to mouse and 79% identity with rabbit heavy chain sequences (1). Differences from previously published DNA and protein seq...

Antibody repertoires are known to be shaped by selection for antigen binding. Unexpectedly, we now show that selection also acts on a non-antigen-binding antibody region: the heavy-chain variable (VH)-encoded "elbow" between variable and constant domains. By sequencing 2.8 million recombined heavy-chain genes from immature and mature B-cell subsets in mice, we demonstrate a striking gradient in...

Immunoglobulins are heterodimeric proteins composed of 2 heavy and 2 light chains. They can be separated functionally into variable domains that bind antigens and constant domains that specify effector functions, such as activation of complement or binding to Fc receptors. The variable domains are created by means of a complex series of gene rearrangement events and can then be subjected to som...

To determine the chemical basis for rabbit heavy chain allotypes, amino acid analyses were carried out on IgG and IgM antibodies isolated from rabbits which were homozygous a1 or a3 for the gamma chain locus and homozygous b4 for the light chain locus. The compositional differences between a1 and a3 IgM antibodies were found to be identical to those between their IgG counterparts. The identity ...

Immunoglobulin heavy chains of myeloma proteins from dogs and cata have been subjected to automated sequence analysis. When the results were compared with human heavy-chain sequences, all the dog and cat proteins could be unequivocally assigned to the V(H)III subgroup. This pattern contrasts with that in human proteins in which only 25% of all heavy chains sequenced belong to this subgroup. The...